The present invention relates to use of vitamin E to normalize blood coagulation during the oral intake of high unsaturated fatty acids of omega-3 type ("omega-3 fatty acids") i.e., fatty acids that have a double bond between carbons 3 and 4 such as eicosa-pentanoic acid ("EPA") and docosahexanoic acid "DHA"). In the context of the present invention, "high" unsaturated fatty acids are those that comprise 3 to 6 preferably 5 to 6 double bonds and 18 to 22 preferably 20 to 22 carbon atoms.
In the 1960s and 1970s, the eating habits of Eskimos in Greenland were studied to determine if a relationship existed between the food they consumed and an observed, low rate of myocardial and brain infarctions. A relationship between consumption of fish oil and the low rate of infarctions was found to exist.
Studies of fish oil revealed that its major constituent was high unsaturated fatty acids of omega-3 type, especially EPA and DHA. Further studies revealed that upon ingestion, EPA and DHA, instead of arachidonic acid ("AA"), also known as eicosatetranoic acid, became integrated into the platelet membranes, thereby reducing platelet aggregation and changing the rheological properties of the blood in a positive way, resulting in less infarction. Coincidental with the use of such fatty acids, formation of anti-inflammatory leukotrienes, and a reduction in blood sugar levels and in increases in blood pressure were observed.
A significant finding relating to the risk of infarction is that, with continuous use of the abovementioned fatty acids in quantities of about 50-1000 mg/day, blood cholesterol levels were reduced as much as 35% and blood triglyceride levels were reduced as much as 58%. Reduction in blood cholesterol level refers, in particular, to reduction in low density lipoproteins ("LDL") and a corresponding increase in high density lipoproteins ("HDL"), which counteract infarction.
A side effect of their fish diet is an increased tendency among the Eskimos to bleed, as reported by Saynor and Varell, Medical Science 8: 379 (1980). These authors were unable to find in the Eskimos, however, any sigificant change in partial thromboplastin time ("PTT") or in thrombin coagulation time. In contrast, Terano et al, Atherosclerosis, 46: 321-331 (1983), found a significant increase in prothrombin time ("PT"), from 11.5 to 12.6 seconds, but no significant changes in PTT, cholesterol phospholipid, HDL-cholesterol, malondialdehyde and vitamin E levels in the serum of these Eskimos.
Based upon an examination of over one hundred patients given high unsaturated fatty acids such as EPA and/or DHA in quantities of up to 1000 mg/day, over a period of four or more weeks, it was found that the PT of these patients, measured as a "Quick value," dropped below that of an untreated patient, resulting in a reduction to 45% below normal.
For purposes of this description, the phrase "Quick value" is used to denote normal prothrombin time, measured with diluted plasma of healthy persons (i.e., 12 seconds), divided by a test subject's prothrombin time. Prothrombin time is measured in accordance with conventional laboratory methods. In essence, citrated plasma is mixed with a surplus of thrombokinase and calcium chloride, and time required for coagulation is measured. An increase in prothrombin time, therefore, is equivalent to a decrease in Quick value.
For patients undergoing treatment with anticoagulants such as indandiones and dicumaroles, use of high unsaturated fatty acids can intensify the effect of anticoagulants, and can lead to a fast drop in Quick value to beyond a therapeutically safe limit, necessitating discontinuation of anticoagulants. Omega-3 fatty acids are used not only under direct medical supervision in the treatment of acute illnesses but also prophylactically by the lay public, without medical supervision, as dietetic supplements. Accordingly, the above-described risk is considerable.
Consequently, it would be desirable if there is some way in which blood coagulation, measured as PT, can be normalized despite a person's use or consumption of a high dose of high unsaturated fatty acids like EPA and DHA.